Retrospective analysis-based prioritization and degradation pattern characterization of sudden unexplained death...

Area of Science:

• Forensic Genetics
• Molecular Pathology
• Transcriptomics

Background:

• Genetic factors play a role in sudden unexplained death (SUD).
• Molecular autopsy is crucial for SUD diagnosis, but validating non-coding variants is challenging.
• Transcriptome analysis is hindered by post-mortem mRNA degradation in myocardial tissues.

Purpose of the Study:

• To develop a method for interpreting transcriptome data in the forensic investigation of SUD.
• To characterize RNA degradation patterns of SUD susceptibility genes in post-mortem tissues.
• To assess the feasibility of using transcriptome analysis alongside molecular autopsy for SUD diagnosis.

Main Methods:

• Retrospective analysis prioritized SUD susceptibility genes.
• Transcriptome data from 432 left ventricle tissues were analyzed for gene degradation patterns.
• RNA degradation differences between unfrozen and thawed samples were investigated.
• Partial least squares-discriminant analysis was used to differentiate gene expression between normal and simulated SUD cases.

Main Results:

• Specific degradation patterns were identified for prioritized SUD susceptibility genes.
• RNA degradation varied between unfrozen and thawed samples.
• A statistical model effectively recognized expression differences in targeted genes based on degradation patterns.
• The proposed strategy enables interpretation of RNA profiling in SUD forensic investigations.

Conclusions:

• A novel strategy facilitates the interpretation of RNA profiling in sudden unexplained death (SUD) investigations.
• Understanding gene degradation patterns is key to utilizing transcriptome data from post-mortem samples.
• This approach enhances the diagnostic capabilities of molecular autopsy in SUD cases.